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Published April 17, 2009 | Accepted Version + Supplemental Material
Journal Article Open

Optical Deconstruction of Parkinsonian Neural Circuitry


Deep brain stimulation (DBS) is a therapeutic option for intractable neurological and psychiatric disorders, including Parkinson's disease and major depression. Because of the heterogeneity of brain tissues where electrodes are placed, it has been challenging to elucidate the relevant target cell types or underlying mechanisms of DBS. We used optogenetics and solid-state optics to systematically drive or inhibit an array of distinct circuit elements in freely moving parkinsonian rodents and found that therapeutic effects within the subthalamic nucleus can be accounted for by direct selective stimulation of afferent axons projecting to this region. In addition to providing insight into DBS mechanisms, these results demonstrate an optical approach for dissection of disease circuitry and define the technological toolbox needed for systematic deconstruction of disease circuits by selectively controlling individual components.

Additional Information

© 2009 American Association for the Advancement of Science. Received for publication 13 October 2008. Accepted for publication 20 February 2009. K.D. is supported by the Kinetics Foundation, the William M. Keck Foundation, the Snyder Foundation, the Albert Yu and Mary Bechmann Foundation, and the Wallace Coulter Foundation, as well as by California Institute for Regenerative Medicine, the McKnight Foundation, the Esther A. and Joseph Klingenstein Fund, NSF, National Institute of Mental Health, National Institute on Drug Abuse, and the NIH Pioneer Award. V.G. is supported by SGF and SIGF (Stanford Graduate Fellowships). M.M is supported by Bio-X and SGF Fellowships. K.R.T. is supported by NARSAD. J.M.H is supported by the Coulter Foundation, the John Blume Foundation and the Davis Phinney Foundation. We especially thank A. M. Aravanis for mentoring and advice on animal surgery and in vivo recordings, F. Zhang and H. C. Tsai for assistance with Cre-dependent opsin targeting, L. Meltzer for useful discussion, advice and help on immunohistochemistry, G. Feng and G. Augustine for collaboration on generation of the Thy-1 mice (available at the Jackson Laboratory), and V. Sohal for help with power spectra analysis. We also thank the entire Deisseroth lab for useful discussions. The materials and methods described herein are freely distributed and supported by the authors (www.stanford.edu/group/dlab).

Attached Files

Accepted Version - nihms-1049500.pdf

Supplemental Material - Gradinaru.SOM.pdf


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August 20, 2023
October 20, 2023